Mendelian Randomization Analysis Support Causal Associations of HbA1c with Circulating Triglyceride, Total and Low-density Lipoprotein Cholesterol in a Chinese Population

Abstract

Previous observational studies supported a positive association of glycated hemoglobin A1c (HbA1c) level with serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). However, the causal relationship between HbA1c and either one of them was unclear in the East Asians. We performed a Mendelian Randomization (MR) analysis in a community-based study sample in Shanghai, China (n = 11,935). To clarify the cause-and-effect relationships of HbA1c with the four interested lipids, an Expanded HbA1c genetic risk score (GRS) with 17 HbA1c-related common variants and a Conservative score by excluding 11 variants were built and adopted as the Instrumental Variables (IVs), respectively. The Expanded HbA1c-GRS was associated with 0.19 unit increment in log-TG ( P = 0.009), 0.42 mmol/L TC ( P = 0.01), and 0.33 mmol/L LDL-C ( P = 0.01); while the Conservative HbA1c-GRS was associated with 0.22 unit in log-TG ( P = 0.03), 0.60 mmol/L TC ( P = 0.01), and 0.51 mmol/L LDL-C ( P = 0.007). No causal relationship was detected for HDL-C. Sensitivity analysis supported the above findings. In conclusions, MR analysis supports a causal role of increased HbA1c level in increment of circulating TG, TC, and LDL-C in a Chinese population.

Glycemic Control of Diabetes Mellitus Patients in Referral Hospitals of Amhara Region, Ethiopia: A Cross-Sectional Study

“…One mg/dl increase in the total cholesterol level of the patient increases the HbA1c by 0.007%. This finding agrees with the Asians research results [ 44 ]. This is due to the poor dietary habits of patients with a high total cholesterol level [ 45 ].…”